Extracorporeal pathogen reduction system

Abstract

The invention relates to an apparatus system and methods for treatment of virus-infected or pathogen-loaded human blood components separated from normal components comprising a separation apparatus and treatment apparatus system that inactivate pathogens in an extracorporeal blood system.

Description

RELATIONSHIP TO COPENDING APPLICATIONS [0001] This patent application is a continuation-in-part application of Ser. No. 10 / 720,811, filed Nov. 24, 2003 entitled “Extracorporeal Pathogen Reduction System”, which is a continuation-in-part application of Ser. No. 10 / 195,814, filed Jul. 15, 2002 entitled “Methods and Apparatus for Enhanced Apheresis”, which is a continuation-in-part application of Ser. No. 09 / 496,613, filed Feb. 2, 2000, entitled “Method and Apparatus for Enhanced Plasmapheresis”, now U.S. Pat. No. 6,423,023, the entire contents of each of which are incorporated herein by reference.TECHNICAL FIELD OF THE INVENTION [0002] The present invention generally relates to medical apparatus and methods for treating body fluid, plasma or blood infected with infectious agents, such as virus, bacteria, and fungi. More particularly, the invention relates to an apparatus system and methods for treatment of virus-infected human blood components separated from normal components comprisi...

AI Technical Summary

Benefits of technology

[0026] Enhanced continuous plasmapheresis is accomplished by continually feeding a blood supply through a filtration chamber to effect separation of plasma components and cellular components. The blood passes in essentially parallel manner to the plane of the filtration membrane at flow rates sufficient to create shear stress across the membrane in the order of 10 to 2,000 dynes / cm2, a preferred range being from about 100 to about 1,000 dynes / cm2. In one aspect, the membrane has a pore size, pore shape, and cells affinity adequately sufficient to allow the plasma components to pass therethrough but retain cellular components thereon. Generally pore sizes of from 0.2 to 1.0 microns are preferred for plasma or platelet separation. Transmembrane pressure of from about 10 mmHg to about 1,000 mmHg is employed to separate the blood supply into cellular components and plasma fractions. With assistance of the orbital motion of the membrane, the local flow rate and shear stress can be controlled, resulting in a narrower range of the transmembrane pressure that has lower hemolysis and lower plugging propensity.

[0028] The term “orbital motion”, when used herein, refers to a motion that moves back and forth between two points in a continuous manner, wherein the route of the backward movement may either partially overlap or not overlap the route of the forward movement. However, the “orbital motion” is different from “rotation” as referred and defined in this patent application. “Rotation” is defined as a movement in such a way that all particles follow circles with a common angular velocity about a common axis. (Webster's New Collegiate Dictionary, G & C Merriam Co. 1980). A membrane device with orbital motion substantially reduces concentration polarization disadvantages of a centrifugation device.

[0033] Some aspects of the invention relate to a method of extracorporeally reducing pathogen burden of a patient comprising: filtering the patient's blood through a blood filtration apparatus configured for separating a plasma constituent from the blood; passing the plasma constituent through pathogen-reduction means for reducing the pathogen burden in the plasma constituent; and returning cellular components of the patient's blood back to the patient. In one embodiment, the filtering step is carried out with the blood filtration apparatus comprising a chamber having a hollow interior enclosed by a first plate, a second plate, and a flexible seal element between the first plate and the second plate, wherein the first plate is either essentially parallel to or at an acute angle to the second plate so as to form a chamber gap for the hollow interior; means for directing blood into the chamber gap; a non-rotational drive structure; the second plate comprising the filter membrane means for separating plasma constituent from the blood, wherein the second plate is detachably coupled to the non-rotational drive structure that controls the second plate in an orbital motion in reference to a center axis of the first plate; a collecting means; means for directing the plasma constituent passing through the filter membrane means to the collecting means; and means for directing from the chamber gap a remaining constituent of the blood out of the chamber.

Problems solved by technology

The separation of blood into cellular component fractions and plasma fractions has inherently some difficulties and complications.

If cellular components are not handled correctly, the cells may lose their functionality and become useless.

In any plasmapheresis-type process effected by ultrafiltration there are various problems which occur during the fractionating of the blood by passing it in a parallel flow pattern over a membrane surface, with a transmembrane pressure sufficient to push the plasma portion of the blood therethrough, while allowing the cellular component portion of the blood to remain thereon.

One of these problems is that the flow rates must be controlled fairly closely.

Thus, if the flow rate employed is too fast at any moment or at any specific region, detrimental turbulence may occur and excess shear force may cause unwanted hemolysis resulting in general destruction of cellular components.

On the other hand, if the flow rate and the transmembrane pressure are not controlled adequately the cellular and macromolecular components of the blood would tend to clog up the membrane thus significantly slowing the ultrafiltration rate.

Such clogging can also cause hemolysis to occur.

Though the average flow rate of the disclosed device is within the non-hemolysis range, the local flow rate and its shear force at any moment and / or at any specific region of the filter membrane may not be adequate to effect the most efficient plasmapheresis.

There are complex issues in designing and operating such a unit.

Further, Solomon et al. device requires enormous membrane surfaces for blood plasma separation which appear not economically practical.

During high centrifugal rotation, a portion of the cellular components may undesirably remain in the rotational device or inside pores of the filter membrane for a prolonged time and may subject to hemolysis, cellular damage or membrane clogging.

The requirement of a proper shear force at the outermost region in a rotational separator apparently limits the size, and therefore the capacity, of the separation apparatus or the spinner.

The centrifuge-type separation apparatus also generally suffers concentration polarization disadvantages.

The pulsatile flow is known to cause certain degrees of turbulence as the pulsatile flow rate changes constantly which may possibly cause cell damage and membrane clogging.

This additional equipment setup and control mechanism for repetitively reversing the transmembrane pressure difference makes this process less economically attractive.

The virus attacks the immune system and leaves the body vulnerable to a variety of life-threatening illnesses and cancers.

Common bacteria, yeast, parasites, and viruses that ordinarily do not cause serious disease in people with fully functional immune systems can cause fatal illnesses in people with AIDS.

Naficy also discloses using diethyl ether to dissolve or destroy the lipid envelope of HIV, thereby destroying the glycoprotein spikes and rendering the virus unable to penetrate and infect the healthy cells.

Though it is known in the prior art that alcohol, ether, hydrocarbons, or combination thereof is feasible in de-virusing the plasma, none of the above-cited prior art discloses a separation apparatus and methods under an orbital motion that has optimal local shear forces and desired quality flow output for the intended HIV delipidation therapy.

Hildreth fails to disclose a method or system for treating a patient infected with the sexually transmitted pathogen or cells susceptible to the pathogen to extend the patient's quality of life.

These materials, although of fairly low toxicity, do have some toxicity e.g. to red blood cells.

However, neither patent nor combination thereof discloses a blood separating system with desired hemolysis quality at a desired separation efficiency due to its concentration polarization and non-uniform flow over the membrane.

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